My understanding was that Efavirenz plus two NRTI's leads to increased fat loss when compared to the other two therapy groups. Is that correct? Is Atripla one of the Efavirenz + two NRTI's groups? I ask because I'm on Atripla and I am afraid of developing lipodistrophy or lipoatrophy.

Thanks

Response from Dr. Frascino

Hi,

You correctly outlined the three arms of ACTG study A5142 that evaluated 753 patients (i.e. large study), examining a variety of metabolic complications. Recently, data was released from an analysis of the results of that study that looked at lipoatrophy of the extremities. The results did surprise many of us. However, I must point out there are always dangers from drawing conclusions based solely on the results of a single study. With that caution in mind, what the study showed was:

2. Stavudine (d4T/Zerit) produces more lipoatrophy of the extremities than zidovudine (AZT/Retrovir), which in turn produces more lipoatrophy of the extremities than tenofovir (Viread).

3. Efavirenz did not exert a demonstrable lipoatrophic effect when combined with lopinavir/ritonavir (Kaletra) when no NRTIs were involved. This suggests that the effect is dependent on the presence of NRTIs, rather than a direct effect of efavirenz. Alternatively, another potential explanation would be partial protective effect of lopinavir/ritonavir.

I must also point out this data analysis was an "intent-to-treat" analysis and therefore before firm conclusions can be drawn, it will be important to measure "on-treatment" results to better understand the association between specific drug combinations and lipoatrophy.

On to your specific question: is Atripla NOT GOOD? Certainly it's proven itself to be both a convenient and effective anti-HIV therapy. In a different recent study, the efavirenz (Sustiva) containing arm was more effective in controlling HIV than the lopinavir/ritonavir (Kaletra) arm. From a "fear of lipoatrophy" perspective, there is now at least some preliminary evidence to suggest efavirenz combined with non-thymidine nucleosides, such as tenofovir, abacavir and emtricitabine, makes sense in terms of decreased chance of lipoatrophy compared to efavirenz combined with zidovudine (AZT) and/or stavudine (d4T).

Should you consider a switch in therapy? This particular study did not address the specific question you raise. It was designed primarily to look at efavirenz versus lopinavir/ritonavir when combined with 2 NRTIs or combined with each other. What can be teased out from the results (intent-to-treat analysis) is that 88% of the patients on a regimen that contained efavirenz plus tenofovir did not develop major fat loss compared to only 60% on the efavirenz plus zidovudine/lamivudine.

Finally, it's equally important to note that the efavirenz plus two NRTIs group had better virologic results than lopinavir/ritonavir plus two NRTIs in this study.

Taken together, all this information can be confusing. Consequently, I encourage you to discuss your individual situation with your HIV specialist. He or she is best equipped to discuss the pros and cons of all treatment options as they relate to your specific circumstances. And that is what his most critical in selecting a regimen. There is no perfect HIV regimen. They all have their potential risks and benefits. Balancing those risks and benefits requires both the art and science of being an HIV specialist.

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